In this project the kinetics of C-peptide will be studied in relation to that of insulin. Four sets of experiments will be performed in conscious dogs with sampling catheters chronically implanted in the portal and hepatic veins and femoral artery. 1) The hepatic metabolism of endogneously secreted C-peptide and insulin will be measured under basal steady state conditions as well as after stimulation of insulin secretion by oral glucose, oral protein and intravenous glucose. 2) The hepatic metabolism of exogenously infused C-peptide and insulin and the renal metabolism of infused C-peptide and insulin will be compared with the metabolism of endogenously secreted peptides. The relationship of urinary C-peptide to portal and peripheral C-peptide concentrations will be defined. 3) C-peptide and insulin will be infused intraportally in equimolar concentrations. The infusion rates calculated from mathematical analysis of peripheral C-peptide levels will be compared with known infusion rates. Intraportal infusions of human and dog C-peptide will be compared. 4) Insulin and C-peptide secretion rates based on portal arterial concentration differences and hepatic plasma flow measurements will be compared with secretion rates calculated mathematically from peripheral levels only. In complementary experiments to be performed in human subjects the metabolic clearance rate of exogenously infused biosynthetic human C-peptide will be measured. The accuracy with which peripheral C-peptide concentrations can be used to predict C-peptide infusion rates will be evaluated. In an additional project, the nature of the components of circulating somatostatin-like immunoreactivity will be characterized in normal control subjects as well as patients with chronic renal failure, cirrhosis, medullary carcinoma of the thyroid and patients who have undergone pancreatectomy. Changes after a standard mixed meal and oral glucose ingestion will also be defined.